Through a breeding program we have developed two herds of Hereford cattle with different hypoxic pulmonary pressor responses which, we believe, will serve as suitable animal models for studies of hypoxic pulmonary hypertension. When chronically exposed to high altitude, one group (susceptible) develops severe pulmonary hypertension and right heart failure while the other (resistant) shows only a moderate rise in pulmonary arterial pressure. The animals separate along similar lines when exposed to acute hypoxia, i.e., 2 hours at a simulated altitude of 4572 m. It has been shown that these characteristics are genetically transmitted from parent to offspring. Differences in ventilation and its control or differences in intrinsic pulmonary vascular reactivity are considered a likely basis for the different responses of susceptible and resistant cattle to hypoxia. The study proposes to investigate these two factors in progeny of the resistant and susceptible herds of cattle. Response curves to carbon dioxide and isocapnic hypoxin will be determined for each animal followed by a study of their ventilatory and pulmonary pressor responses to acute and chronic hypoxia. Histologic determinations of lung vessel smooth muscle and pulmonary hemodynamic responses to vasodilator and vasoconstrictor drugs, high and low oxygen will be used in assessing the two groups of offspring for pulmonary vascular reactivity. We also propose to make preliminary investigations into miniature swine as a second genetic animal model of hypoxic pulmonary hypertension. Minipigs offer the advantages of being more prolific and having a shorter generation time than cattle. Results of the study could have significant implications in terms of human and animal health.